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黄芪通过上调肌浆网钙ATP酶2a(SERCA2a)的表达改善阿霉素损伤大鼠心脏的心脏功能。

Astragalus Improved Cardiac Function of Adriamycin-Injured Rat Hearts by Upregulation of SERCA2a Expression.

作者信息

Su Dan, Li Han-Yi, Yan Hao-Ran, Liu Peng-Fei, Zhang Liu, Cheng Jian-Hua

机构信息

Department of Pharmacology, School of Medicine, Tongji University, Shanghai 200092, China.

出版信息

Am J Chin Med. 2009;37(3):519-29. doi: 10.1142/S0192415X09007028.

Abstract

The traditional Chinese medical herb Astragalus, the dried root of Astragalus membranaceus (Fisch.) Bge., has been widely applied to treat patients with cardiovascular disease in China and has profound cardioprotective effects. This study investigated the effect of Astragalus on hemodynamic changes in adriamycin (ADR)-injured rat hearts and its underlying molecular mechanism. Sprague-Dawley rats were divided into four groups: control, ADR only, ADR + low dose of Astragalus and ADR + high dose of Astragalus. Rats were injected intraperitoneally with 6 equal doses of ADR (cumulative dose, 12 mg/kg) over a period of 2 weeks. Treatment of Astragalus began 1 day before the onset of ADR injection and was given orally once a day for 50 days (3.3 or 10 g/kg/day). Five weeks after the final injection of ADR, rats treated with ADR only showed a significant inhibition of cardiac diastolic function accompanied by the presence of ascites, a remarkable reduction in body weight and heart weight as well as survival rate compared to the controls. Moreover, SERCA2a mRNA and protein expressions in hearts were obviously downregulated by ADR. However, this impaired cardiac function was significantly improved in both doses of Astragalus feeding groups. The amount of ascites was also reduced in a similar extent in these 2 groups. Only the high dose treatment of Astragalus significantly attenuated the changes of SERCA2a expression in injured hearts and improved survival. These results indicated that Astragalus could improve cardiac function of ADR-injured rat hearts, which was partly mediated by upregulation of SERCA2a expression.

摘要

传统中药黄芪,即膜荚黄芪(Fisch.)Bge. 的干燥根,在中国已被广泛用于治疗心血管疾病患者,并具有深远的心脏保护作用。本研究调查了黄芪对阿霉素(ADR)损伤大鼠心脏血流动力学变化的影响及其潜在分子机制。将Sprague-Dawley大鼠分为四组:对照组、仅ADR组、ADR + 低剂量黄芪组和ADR + 高剂量黄芪组。在2周内给大鼠腹腔注射6次等量的ADR(累积剂量,12 mg/kg)。黄芪治疗在ADR注射开始前1天开始,每天口服给药1次,持续50天(3.3或10 g/kg/天)。在最后一次注射ADR 5周后,仅接受ADR治疗的大鼠与对照组相比,心脏舒张功能受到显著抑制,伴有腹水、体重、心脏重量以及存活率显著降低。此外,ADR明显下调了心脏中SERCA2a mRNA和蛋白的表达。然而,在两个黄芪给药组中,这种受损的心脏功能均得到显著改善。这两组中的腹水数量也有类似程度的减少。只有高剂量黄芪治疗显著减轻了受损心脏中SERCA2a表达的变化并提高了存活率。这些结果表明,黄芪可以改善ADR损伤大鼠心脏的功能,这部分是通过上调SERCA2a表达介导的。

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